Low levels of RNA linked to schizophrenia

Australian scientists have described how some neurons in the brain switch off certain genes as part of normal brain function, a process that appeared disturbed in people with schizophrenia.

While most people were familiar with the role DNA played instructing the body’s cells to produce proteins, a far greater amount of genetic material, called non-coding RNA, was involved in regulating the expression of the genome in response to external cues, such as when neurons fire in the brain.

One of the research leaders, John Mattick, said in the brain, sections of these genes, known as long non-coding RNA, once activated, guided the behaviour of neurons and how they connected to each other.

“In the brain these processes are soft-wired and they respond and adapt to external cues,” said Professor Mattick, the executive director of the Garvan Institute of Medical Research.

Over the past two decades Professor Mattick and other others have shown the body’s vast amounts of non-coding RNA are not junk as previously thought, but essential to regulating the function of other genes.

“People have misunderstood the structure of human genetic programming for the past 50 years,” he said.

“The evidence is very strong that most of the human genome is active in producing RNA, most of which controls and regulates the genome in very precise ways during development.”

In this study, Professor Mattick and Dr Guy Barry from the Institute for Molecular Bioscience at the University of QLD, found that when they activated specific neurons, the level of long non-coding RNA, known as Gomafu, inside the cell dropped dramatically, which signalled to other parts of the cell to perform specific functions.

After a few hours, the Gomafu levels return to normal, ready to be activated again.

But in the post-mortem brains of people with schizophrenia, the researchers found abnormally low levels of Gomafu.

While other experiments with colleagues from Johns Hopkins University showed these non-coding genes could form strong bonds with other proteins inside the neuron that have previously been implicated in schizophrenia.

“You can imagine that if the schizophrenic brain is firing differently – and Gomafu levels are consistently lower – it would cause havoc within the cell, with all sorts of genes and proteins free floating and available to act, where in a normal brain they would be tethered to Gomafu.”

The team, whose findings were published in the journal Molecular Psychiatry, plan to study these process in more detail in human cells.